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dc.contributor.authorTrotschel, Christian  Concept link
dc.contributor.authorHamzeh, Hussein  Concept link
dc.contributor.authorAlvarez, Luis  Concept link
dc.contributor.authorPascal, René  Concept link
dc.contributor.authorLavryk, Fedir  Concept link
dc.contributor.authorBönigk, Wolfgang  Concept link
dc.contributor.authorKörschen, Heinz Gerd  Concept link
dc.contributor.authorMüller, Astrid  Concept link
dc.contributor.authorPoetsch, Ansgar  Concept link
dc.contributor.authorRennhack, Andreas  Concept link
dc.contributor.authorGui, Long  Concept link
dc.contributor.authorNicastro, Daniela  Concept link
dc.contributor.authorStrünker, Timo  Concept link
dc.contributor.authorSeifert, Reinhard  Concept link
dc.contributor.authorKaupp, U. Benjamin  Concept link
dc.date.accessioned2020-04-07T19:19:34Z
dc.date.available2020-04-07T19:19:34Z
dc.date.issued2019-12-27
dc.identifier.citationTroetschel, C., Hamzeh, H., Alvarez, L., Pascal, R., Lavryk, F., Boenigk, W., Koerschen, H. G., Mueller, A., Poetsch, A., Rennhack, A., Gui, L., Nicastro, D., Struenker, T., Seifert, R., & Kaupp, U. B. (2020). Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation. Embo Journal, 39(4), e102723.en_US
dc.identifier.urihttps://hdl.handle.net/1912/25612
dc.description© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Troetschel, C., Hamzeh, H., Alvarez, L., Pascal, R., Lavryk, F., Boenigk, W., Koerschen, H. G., Mueller, A., Poetsch, A., Rennhack, A., Gui, L., Nicastro, D., Struenker, T., Seifert, R., & Kaupp, U. B. Absolute proteomic quantification reveals design principles of sperm flagellar chemosensation. Embo Journal, 39(4), (2020): e102723, doi:10.15252/embj.2019102723.en_US
dc.description.abstractCilia serve as cellular antennae that translate sensory information into physiological responses. In the sperm flagellum, a single chemoattractant molecule can trigger a Ca2+ rise that controls motility. The mechanisms underlying such ultra‐sensitivity are ill‐defined. Here, we determine by mass spectrometry the copy number of nineteen chemosensory signaling proteins in sperm flagella from the sea urchin Arbacia punctulata. Proteins are up to 1,000‐fold more abundant than the free cellular messengers cAMP, cGMP, H+, and Ca2+. Opto‐chemical techniques show that high protein concentrations kinetically compartmentalize the flagellum: Within milliseconds, cGMP is relayed from the receptor guanylate cyclase to a cGMP‐gated channel that serves as a perfect chemo‐electrical transducer. cGMP is rapidly hydrolyzed, possibly via “substrate channeling” from the channel to the phosphodiesterase PDE5. The channel/PDE5 tandem encodes cGMP turnover rates rather than concentrations. The rate‐detection mechanism allows continuous stimulus sampling over a wide dynamic range. The textbook notion of signal amplification—few enzyme molecules process many messenger molecules—does not hold for sperm flagella. Instead, high protein concentrations ascertain messenger detection. Similar mechanisms may occur in other small compartments like primary cilia or dendritic spines.en_US
dc.description.sponsorshipWe thank Heike Krause for preparing the manuscript. Financial support by the Deutsche Forschungsgemeinschaft (DFG) via the priority program SPP 1726 “Microswimmers” and the Cluster of Excellence 1023 “ImmunoSensation” is gratefully acknowledged. We thank D. Stoddard for management of the UTSW cryo‐electron microscope facility, which is funded in part by a Cancer Prevention and Research Institute of Texas (CPRIT) Core Facility Award (RP170644). This study was supported by HHS|National Institutes of Health (NIH) grant R01 GM083122 and by CPRIT grant RR140082 to D. Nicastro.en_US
dc.publisherEMBO Pressen_US
dc.relation.urihttps://doi.org/10.15252/embj.2019102723
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectciliumen_US
dc.subjectelectron tomographyen_US
dc.subjectfertilizationen_US
dc.subjectquantitative mass spectrometryen_US
dc.subjectsignalingen_US
dc.titleAbsolute proteomic quantification reveals design principles of sperm flagellar chemosensationen_US
dc.typeArticleen_US
dc.identifier.doi10.15252/embj.2019102723


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International